Carryl Heather, Swang Melanie, Lawrence Jerome, Curtis Kimberly, Kamboj Herman, Van Rompay Koen K A, De Paris Kristina, Burke Mark W
§California National Primate Research Center, University of California at Davis, Davis, California 95616, United States.
∥Department of Microbiology and Immunology and Center for AIDS Research School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
ACS Chem Neurosci. 2015 Aug 19;6(8):1276-89. doi: 10.1021/acschemneuro.5b00044. Epub 2015 Jun 19.
Pediatric human immunodeficiency virus (HIV-1) infection remains a global health crisis. Children are much more susceptible to HIV-1 neurological impairments than adults, which can be exacerbated by coinfections. Neurological characteristics of pediatric HIV-1 infection suggest dysfunction in the frontal cortex as well as the hippocampus; limited MRI data indicate global cerebral atrophy, and pathological data suggest accelerated neuronal apoptosis in the cortex. An obstacle to pediatric HIV-1 research is a human representative model system. Host-species specificity of HIV-1 limits the ability to model neurological consequences of pediatric HIV-1 infection in animals. Several models have been proposed including neonatal intracranial injections of HIV-1 viral proteins in rats and perinatal simian immunodeficiency virus (SIV) infection of infant macaques. Nonhuman primate models recapitulate the complexity of pediatric HIV-1 neuropathogenesis while rodent models are able to elucidate the role specific viral proteins exert on neurodevelopment. Nonhuman primate models show similar behavioral and neuropathological characteristics to pediatric HIV-1 infection and offer a stage to investigate early viral mechanisms, latency reservoirs, and therapeutic interventions. Here we review the relative strengths and limitations of pediatric HIV-1 model systems.
小儿人类免疫缺陷病毒（HIV-1）感染仍然是一场全球卫生危机。儿童比成人更容易受到HIV-1神经损伤的影响，合并感染会使这种情况更加恶化。小儿HIV-1感染的神经学特征表明额叶皮质以及海马体存在功能障碍；有限的MRI数据显示全脑萎缩，病理数据表明皮质中神经元凋亡加速。小儿HIV-1研究的一个障碍是缺乏具有人类代表性的模型系统。HIV-1的宿主物种特异性限制了在动物中模拟小儿HIV-1感染神经学后果的能力。已经提出了几种模型，包括在大鼠中新生儿颅内注射HIV-1病毒蛋白以及对幼年猕猴进行围产期猿猴免疫缺陷病毒（SIV）感染。非人灵长类动物模型概括了小儿HIV-1神经发病机制的复杂性，而啮齿动物模型能够阐明特定病毒蛋白对神经发育的作用。非人灵长类动物模型显示出与小儿HIV-1感染相似的行为和神经病理学特征，并为研究早期病毒机制、潜伏库和治疗干预提供了一个平台。在此，我们综述了小儿HIV-1模型系统的相对优势和局限性。
